438 research outputs found

    Reaction of P-halogeno-phospha-alkenes with alkene complexes of nickel and platinum: η2-co-ordination and unusual oxidative addition behaviour

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    Phospha-alkenes X-P=CTMS2(X = F, Cl, I; TMS = SiMe3) display different reaction behaviour towards metal complexes (Bu3P)2Ni(cod)(cod = cyclo-octa-1,5-diene) or (Ph3P)2Pt(C2H4), respectively, undergoing either co-ordination to give η2-phospha-alkene complexes or alternatively oxidative addition of the P-X bond, forming phospha-alkenyl-metal(II) complexes, [(R3P)2M(X)(σ-P=CTMS2)]

    Evaluation of Oklahoma pavement design procedures phase I - interim report (84-60)

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    This report covers collection of pavement conditions and other pertinent performance data for 6 representative pavement sites that have failed prematurely and 2 sites which have performed as intended. Interviews of Oklahoma DOT personnel, 1 review of records, inspection by an expert diagnostic team together with a field data collection program are also included. Based upon this data as well as laboratory testing and analysis of the deflection testing performed, an assessment of the causes for early failures at the representative sites are made. Recommendations for changes in design and construction practices to prevent future premature pavement failures are included.Draft Interim Phase IN

    Clinical evaluation of magnetic resonance imaging in coronary heart disease: The CE-MARC study

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    <p>Abstract</p> <p>Background</p> <p>Several investigations are currently available to establish the diagnosis of coronary heart disease (CHD). Of these, cardiovascular magnetic resonance (CMR) offers the greatest information from a single test, allowing the assessment of myocardial function, perfusion, viability and coronary artery anatomy. However, data from large scale studies that prospectively evaluate the diagnostic accuracy of multi-parametric CMR for the detection of CHD in unselected populations are lacking, and there are few data on the performance of CMR compared with current diagnostic tests, its prognostic value and cost-effectiveness.</p> <p>Methods/design</p> <p>This is a prospective diagnostic accuracy cohort study of 750 patients referred to a cardiologist with suspected CHD. Exercise tolerance testing (ETT) will be preformed if patients are physically able. Recruited patients will then undergo CMR and single photon emission tomography (SPECT) followed in all patients by invasive X-ray coronary angiography. The order of the CMR and SPECT tests will be randomised. The CMR study will comprise rest and adenosine stress perfusion, cine imaging, late gadolinium enhancement and whole-heart MR coronary angiography. SPECT will use a gated stress/rest protocol. The primary objective of the study is to determine the diagnostic accuracy of CMR in detecting significant coronary stenosis, as defined by X-ray coronary angiography. Secondary objectives include an assessment of the prognostic value of CMR imaging, a comparison of its diagnostic accuracy against SPECT and ETT, and an assessment of cost-effectiveness.</p> <p>Discussion</p> <p>The CE-MARC study is a prospective, diagnostic accuracy cohort study of 750 patients assessing the performance of a multi-parametric CMR study in detecting CHD using invasive X-ray coronary angiography as the reference standard and comparing it with ETT and SPECT.</p> <p>Trial Registration</p> <p>Current Controlled Trials ISRCTN77246133</p

    Ultrastructural identification of uncoated caveolin-independent early endocytic vehicles

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    Using quantitative light microscopy and a modified immunoelectron microscopic technique, we have characterized the entry pathway of the cholera toxin binding subunit (CTB) in primary embryonic fibroblasts. CTB trafficking to the Golgi complex was identical in caveolin-1null (Cav1−/−) mouse embryonic fibroblasts (MEFs) and wild-type (WT) MEFs. CTB entry in the Cav1−/− MEFs was predominantly clathrin and dynamin independent but relatively cholesterol dependent. Immunoelectron microscopy was used to quantify budded and surface-connected caveolae and to identify noncaveolar endocytic vehicles. In WT MEFs, a small fraction of the total Cav1-positive structures were shown to bud from the plasma membrane (2% per minute), and budding increased upon okadaic acid or lactosyl ceramide treatment. However, the major carriers involved in initial entry of CTB were identified as uncoated tubular or ring-shaped structures. These carriers contained GPI-anchored proteins and fluid phase markers and represented the major vehicles mediating CTB uptake in both WT and caveolae-null cells

    Coordinated Regulation of SIV Replication and Immune Responses in the CNS

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    Central nervous system (CNS) invasion during acute-stage HIV-infection has been demonstrated in a small number of individuals, but there is no evidence of neurological impairment at this stage and virus infection in brain appears to be controlled until late-stage disease. Using our reproducible SIV macaque model to examine the earliest stages of infection in the CNS, we identified immune responses that differentially regulate inflammation and virus replication in the brain compared to the peripheral blood and lymphoid tissues. SIV replication in brain macrophages and in brain of SIV-infected macaques was detected at 4 days post-inoculation (p.i.). This was accompanied by upregulation of innate immune responses, including IFNβ, IFNβ-induced gene MxA mRNA, and TNFα. Additionally, IL-10, the chemokine CCL2, and activation markers in macrophages, endothelial cells, and astrocytes were all increased in the brain at four days p.i. We observed synchronous control of virus replication, cytokine mRNA levels and inflammatory markers (MHC Class II, CD68 and GFAP) by 14 days p.i.; however, control failure was followed by development of CNS lesions in the brain. SIV infection was accompanied by induction of the dominant-negative isoform of C/EBPβ, which regulates SIV, CCL2, and IL6 transcription, as well as inflammatory responses in macrophages and astrocytes. This synchronous response in the CNS is in part due to the effect of the C/EBPβ on virus replication and cytokine expression in macrophage-lineage cells in contrast to CD4+ lymphocytes in peripheral blood and lymphoid tissues. Thus, we have identified a crucial period in the brain when virus replication and inflammation are controlled. As in HIV-infected individuals, though, this control is not sustained in the brain. Our results suggest that intervention with antiretroviral drugs or anti-inflammatory therapeutics with CNS penetration would sustain early control. These studies further suggest that interventions should target HIV-infected individuals with increased CCL2 levels or HIV RNA in the CNS

    High Frequency of Cytomegalovirus-Specific Cytotoxic T-Effector Cells in HLA-A*0201-Positive Subjects during Multiple Viral Coinfections

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    How the cellular immune response copes with diverse antigenic competition is poorly understood. Responses of virus-specific cytotoxic T lymphocytes (CTL) were examined longitudinally in an individual coinfected with human immunodeficiency virus type 1 (HIV-1), Epstein-Barr virus (EBV), and cytomegalovirus (CMV). CTL responses to all 3 viruses were quantified by limiting dilution analysis and staining with HLA-A*0201 tetrameric complexes folded with HIV-1, EBV, and CMV peptides. A predominance of CMV-pp65-speciflc CTL was found, with a much lower frequency of CTL to HIV-1 Gag and Pol and to EBV-BMLF1 and LMP2. The high frequency of CMV-speciflc CTL, compared with HIV-1- and EBV-specific CTL, was confirmed in an additional 16 HLA-A*0201-positive virus-coinfected subjects. Therefore, the human immune system can mount CTL responses to multiple viral antigens simultaneously, albeit with different strength

    U.S. Army Small Space Update

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    In December 2010, the U.S. Army flew its first satellite in 50 years, the SMDC-ONE CubeSat. Placed in a very low orbit, the first SMDC-ONE mission lasted only 35 days but enjoyed great success in demonstrating the viability of CubeSats to perform exfiltration of unattended ground sensors data and serve as a communications relay between ground stations over 1000 land miles apart. The success of SMDC-ONE helped shape the U.S. Army’s Space and Missile Defense Command’s (SMDC) programmatic goals for finding new and innovative ways to implement space applications and technologies that aid the warfighter. Since 2010, SMDC has flown ten additional CubeSats including the three SMDC Nanosatellite Program-3 (SNaP) CubeSats currently on orbit (launched October 2015). This paper addresses several SMDC satellite-related development efforts including SNaP, Army Resilient Global On-the-move SATCOM (ARGOS) Ka-band communications microsatellites, Kestrel Eye (an imaging microsatellite), Kestrel Eye Ground Station (KEGS), Common Ground Station (CGS) for all future Army small satellites, supporting technologies including Small Business Innovative Research (SBIR) efforts, the Concepts Analysis Laboratory, SMDC Space Laboratory, the ACES RED effort and earlier responsive launch vehicle activities. Several of the lessons learned from previous as well as ongoing satellite activities are also covered
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